Risk Factors for Lateral Margin Positivity Following Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer

Background: Lateral margin positivity (LM+) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) may lead to residual disease and additional treatment. Subepithelial (SE) spread beneath normal mucosa has been suggested as a mechanism, but its association with LM+ is unclear. Methods: We retrospectively reviewed patients who underwent ESD for EGC from 2011 to 2021. Twenty-one LM+ cases were identified, and 227 LM– controls treated in 2019 were selected. Clinicopathologic and endoscopic factors were compared, and multivariate logistic regression was used to identify predictors. SE spread extent was evaluated pathologically. Results: Differentiation, Lauren classification, lesion size, and endoscopic color change were associated with LM+ in univariate analysis. Lesion size ≥ 2 cm was the only independent predictor. SE spread length was greater in LM+ cases than controls (5.80 ± 1.30 mm vs. 2.60 ± 2.36 mm, p = 0.004). SE spread ≥ 5 mm significantly increased the risk of LM+ (OR 15.077, 95% CI 1.550–146.670). Conclusions: SE spread—particularly when ≥5 mm—may contribute to LM+ by obscuring the true tumor boundary. Wider marking and resection margins may be considered in lesions with features suggesting SE spread.